scholarly journals Individual variability in functional connectivity architecture of the mouse brain

2020 ◽  
Author(s):  
Eyal Bergmann ◽  
Xenia Gofman ◽  
Alexandra Kavushansky ◽  
Itamar Kahn

AbstractThe functional organization of brain networks can be estimated using fMRI by examining the coherence of spontaneous fluctuations in the fMRI signal, a method known as resting-state functional connectivity MRI. Previous studies in humans reported that such functional networks are dominated by stable group and individual factors, demonstrating that fMRI is suited to measuring subject-specific characteristics, and suggesting the utility of such precision fMRI approach in personalized medicine. However, mechanistic investigations to the sources of individual variability in health and disease are limited in humans and thus require animal models. Here, we used repeated-measurement resting-state fMRI in awake mice to quantify the contribution of individual variation to the functional architecture of the mouse cortex. Comparing the organization of functional networks across the group, we found dominant common organizational principles. The data also revealed stable individual features, which create a unique fingerprint that allow identification of individual mice from the group. Examining the distribution of individual variation across the mouse cortex, we found it is homogeneously distributed in both sensory and association networks. Finally, connectome-based predictive modeling of motor behavior in the rotarod task revealed that individual variation in functional connectivity explained behavioral variability. Collectively, these results show that mouse functional networks are characterized by individual variations suggesting that individual variation characterizes the mammalian cortex in general, and not only the primate cortex. These findings lay the foundation for future mechanistic investigations of individual brain organization and pre-clinical studies of brain disorders in the context of personalized medicine.

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Eyal Bergmann ◽  
Xenia Gofman ◽  
Alexandra Kavushansky ◽  
Itamar Kahn

AbstractIn recent years precision fMRI has emerged in human brain research, demonstrating characterization of individual differences in brain organization. However, mechanistic investigations to the sources of individual variability are limited in humans and thus require animal models. Here, we used resting-state fMRI in awake mice to quantify the contribution of individual variation to the functional architecture of the mouse cortex. We found that the mouse connectome is also characterized by stable individual features that support connectivity-based identification. Unlike in humans, we found that individual variation is homogeneously distributed in sensory and association networks. Finally, connectome-based predictive modeling of motor behavior in the rotarod task revealed that individual variation in functional connectivity explained behavioral variability. Collectively, these results establish the feasibility of precision fMRI in mice and lay the foundation for future mechanistic investigations of individual brain organization and pre-clinical studies of brain disorders in the context of personalized medicine.


2019 ◽  
Author(s):  
Ting Xu ◽  
Darrick Sturgeon ◽  
Julian S.B. Ramirez ◽  
Seán Froudist-Walsh ◽  
Daniel S. Margulies ◽  
...  

ABSTRACTBackgroundNonhuman primate models (NHP) are commonly used to advance our understanding of brain function and organization. However, to date, they have offered few insights into individual differences among NHPs. In large part, this is due to the logistical challenges of NHP research, which limit most studies to five subjects or fewer.MethodsWe leveraged the availability of a large-scale open NHP imaging resource to provide an initial examination of individual differences in the functional organization of the nonhuman primate brain. Specifically, we selected one awake fMRI dataset (Newcastle: n = 10) and two anesthetized fMRI data sets (Oxford: n = 19; UC-Davis: n = 19) to examine individual differences in functional connectivity characteristics across the cortex, as well as potential state dependencies.ResultsWe noted significant individual variations of functional connectivity across the macaque cortex. Similar to the findings in human, during the awake state, the primary sensory and motor cortices showed lower variability than the high-order association regions. This variability pattern was significantly correlated with T1w/T2w map, the degree of long-distance connectivity, but not short-distance connectivity. However, the inter-individual variability under anesthesia exhibited a very distinct pattern, with lower variability in medial frontal cortex, precuneus and somatomotor regions and higher variability in the lateral ventral frontal and insular cortices.ConclusionsThis work has implications for our understanding of the evolutionary origins of individual variation in the human brain, as well as methodological implications that must be considered in any pursuit to study individual variation in NHP models.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wei-Tang Chang ◽  
Stephanie K. Langella ◽  
Yichuan Tang ◽  
Sahar Ahmad ◽  
Han Zhang ◽  
...  

AbstractThe hippocampus is critical for learning and memory and may be separated into anatomically-defined hippocampal subfields (aHPSFs). Hippocampal functional networks, particularly during resting state, are generally analyzed using aHPSFs as seed regions, with the underlying assumption that the function within a subfield is homogeneous, yet heterogeneous between subfields. However, several prior studies have observed similar resting-state functional connectivity (FC) profiles between aHPSFs. Alternatively, data-driven approaches investigate hippocampal functional organization without a priori assumptions. However, insufficient spatial resolution may result in a number of caveats concerning the reliability of the results. Hence, we developed a functional Magnetic Resonance Imaging (fMRI) sequence on a 7 T MR scanner achieving 0.94 mm isotropic resolution with a TR of 2 s and brain-wide coverage to (1) investigate the functional organization within hippocampus at rest, and (2) compare the brain-wide FC associated with fine-grained aHPSFs and functionally-defined hippocampal subfields (fHPSFs). This study showed that fHPSFs were arranged along the longitudinal axis that were not comparable to the lamellar structures of aHPSFs. For brain-wide FC, the fHPSFs rather than aHPSFs revealed that a number of fHPSFs connected specifically with some of the functional networks. Different functional networks also showed preferential connections with different portions of hippocampal subfields.


2021 ◽  
Author(s):  
Michele Allegra ◽  
Chiara Favaretto ◽  
Nicholas Metcalf ◽  
Maurizio Corbetta ◽  
Andrea Brovelli

ABSTRACTNeuroimaging and neurological studies suggest that stroke is a brain network syndrome. While causing local ischemia and cell damage at the site of injury, stroke strongly perturbs the functional organization of brain networks at large. Critically, functional connectivity abnormalities parallel both behavioral deficits and functional recovery across different cognitive domains. However, the reasons for such relations remain poorly understood. Here, we tested the hypothesis that alterations in inter-areal communication underlie stroke-related modulations in functional connectivity (FC). To this aim, we used resting-state fMRI and Granger causality analysis to quantify information transfer between brain areas and its alteration in stroke. Two main large-scale anomalies were observed in stroke patients. First, inter-hemispheric information transfer was strongly decreased with respect to healthy controls. Second, information transfer within the affected hemisphere, and from the affected to the intact hemisphere was reduced. Both anomalies were more prominent in resting-state networks related to attention and language, and they were correlated with impaired performance in several behavioral domains. Overall, our results support the hypothesis that stroke perturbs inter-areal communication within and across hemispheres, and suggest novel therapeutic approaches aimed at restoring normal information flow.SIGNIFICANCE STATEMENTA thorough understanding of how stroke perturbs brain function is needed to improve recovery from the severe neurological syndromes affecting stroke patients. Previous resting-state neuroimaging studies suggested that interaction between hemispheres decreases after stroke, while interaction between areas of the same hemisphere increases. Here, we used Granger causality to reconstruct information flows in the brain at rest, and analyze how stroke perturbs them. We showed that stroke causes a global reduction of inter-hemispheric communication, and an imbalance between the intact and the affected hemisphere: information flows within and from the latter are impaired. Our results may inform the design of stimulation therapies to restore the functional balance lost after stroke.


2020 ◽  
Vol 14 ◽  
Author(s):  
Benjamin M. Rosenberg ◽  
Eva Mennigen ◽  
Martin M. Monti ◽  
Roselinde H. Kaiser

Prior research has shown that during development, there is increased segregation between, and increased integration within, prototypical resting-state functional brain networks. Functional networks are typically defined by static functional connectivity over extended periods of rest. However, little is known about how time-varying properties of functional networks change with age. Likewise, a comparison of standard approaches to functional connectivity may provide a nuanced view of how network integration and segregation are reflected across the lifespan. Therefore, this exploratory study evaluated common approaches to static and dynamic functional network connectivity in a publicly available dataset of subjects ranging from 8 to 75 years of age. Analyses evaluated relationships between age and static resting-state functional connectivity, variability (standard deviation) of connectivity, and mean dwell time of functional network states defined by recurring patterns of whole-brain connectivity. Results showed that older age was associated with decreased static connectivity between nodes of different canonical networks, particularly between the visual system and nodes in other networks. Age was not significantly related to variability of connectivity. Mean dwell time of a network state reflecting high connectivity between visual regions decreased with age, but older age was also associated with increased mean dwell time of a network state reflecting high connectivity within and between canonical sensorimotor and visual networks. Results support a model of increased network segregation over the lifespan and also highlight potential pathways of top-down regulation among networks.


2020 ◽  
Vol 25 ◽  
pp. 102076 ◽  
Author(s):  
Kristina Miloserdov ◽  
Carsten Schmidt-Samoa ◽  
Kathleen Williams ◽  
Christiane Anne Weinrich ◽  
Igor Kagan ◽  
...  

2011 ◽  
Vol 105 (6) ◽  
pp. 2753-2763 ◽  
Author(s):  
Gaëlle Doucet ◽  
Mikaël Naveau ◽  
Laurent Petit ◽  
Nicolas Delcroix ◽  
Laure Zago ◽  
...  

Spontaneous brain activity was mapped with functional MRI (fMRI) in a sample of 180 subjects while in a conscious resting-state condition. With the use of independent component analysis (ICA) of each individual fMRI signal and classification of the ICA-defined components across subjects, a set of 23 resting-state networks (RNs) was identified. Functional connectivity between each pair of RNs was assessed using temporal correlation analyses in the 0.01- to 0.1-Hz frequency band, and the corresponding set of correlation coefficients was used to obtain a hierarchical clustering of the 23 RNs. At the highest hierarchical level, we found two anticorrelated systems in charge of intrinsic and extrinsic processing, respectively. At a lower level, the intrinsic system appears to be partitioned in three modules that subserve generation of spontaneous thoughts (M1a; default mode), inner maintenance and manipulation of information (M1b), and cognitive control and switching activity (M1c), respectively. The extrinsic system was found to be made of two distinct modules: one including primary somatosensory and auditory areas and the dorsal attentional network (M2a) and the other encompassing the visual areas (M2b). Functional connectivity analyses revealed that M1b played a central role in the functioning of the intrinsic system, whereas M1c seems to mediate exchange of information between the intrinsic and extrinsic systems.


2018 ◽  
Author(s):  
Jonathan F. O’Rawe ◽  
Jaime S. Ide ◽  
Hoi-Chung Leung

AbstractIn accordance with the concept of topographic organization of neuroanatomical structures, there is an increased interest in estimating and delineating continuous changes in the functional connectivity patterns across neighboring voxels within a region of interest using resting-state fMRI data. Fundamental to this functional connectivity gradient analysis is the assumption that the functional organization is stable and uniform across the region of interest. To evaluate this assumption, we developed a model testing procedure to arbitrate between overlapping, shifted, or different topographic connectivity gradients across subdivisions of a structure. We tested the procedure using the striatum, a subcortical structure consisting of the caudate nucleus and putamen, in which an extensive literature, primarily from rodents and non-human primates, suggest to have a shared topographic organization of a single diagonal gradient. We found, across multiple resting state fMRI data samples of different spatial resolutions in humans, and one macaque resting state fMRI data sample, that the models with different functional connectivity gradients across the caudate and putamen was the preferred model. The model selection procedure was validated in control conditions of checkerboard subdivisions, demonstrating the expected overlapping gradient. More specifically, while we replicated the diagonal organization of the functional connectivity gradients in both the caudate and putamen, our analysis also revealed a medial-lateral organization within the caudate. Not surprisingly, performing the same analysis assuming a unitary gradient obfuscates the medial-lateral organization of the caudate, producing only a diagonal gradient. These findings demonstrate the importance of testing basic assumptions and evaluating interpretations across species. The significance of differential topographic gradients across the putamen and caudate and the medial-lateral gradient of the caudate in humans should be tested in future studies.


2020 ◽  
Author(s):  
Niv Tik ◽  
Abigail Livny ◽  
Shachar Gal ◽  
Karny Gigi ◽  
Galia Tsarfaty ◽  
...  

AbstractBACKGROUNDPatients suffering from schizophrenia demonstrate abnormal brain activity, as well as alterations in patterns of functional connectivity assessed by functional magnetic resonance imaging (fMRI). Previous studies in healthy participants suggest a strong association between resting-state functional connectivity and task-evoked brain activity that could be detected at an individual level, and show that brain activation in various tasks could be predicted from task-free fMRI scans. In the current study we aimed to predict brain activity in patients diagnosed with schizophrenia, using a prediction model based on healthy individuals exclusively. This offers novel insights regarding the interrelations between brain connectivity and activity in schizophrenia.METHODSWe generated a prediction model using a group of 80 healthy controls that performed the well-validated N-back task, and used it to predict individual variability in task-evoked brain activation in 20 patients diagnosed with schizophrenia.RESULTSWe demonstrated a successful prediction of individual variability in the task-evoked brain activation based on resting-state functional connectivity. The predictions were highly sensitive, reflected by high correlations between predicted and actual activation maps (Median = 0.589, SD = 0.193) and specific, evaluated by a Kolomogrov-Smirnov test (D = 0.25, p < 0.0001).CONCLUSIONSA Successful prediction of brain activity from resting-state functional connectivity highlights the strong coupling between the two. Moreover, our results support the notion that even though resting-state functional connectivity and task-evoked brain activity are frequently reported to be altered in schizophrenia, the relations between them remains unaffected. This may allow to generate task activity maps for clinical populations without the need the actually perform the task.


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